5550636 IMPROVEMENT IN ACUTE NEUROLOGICAL COMPLICATIONS RELATED TO 50 STEM CELL TRANSPLANT IN SICKLE CELL DISEASE: LESSONS FROM OUR EXPERIENCE
Authors: J.M.S. Jose Manuel Marco Sanchez, M.G.M. Marina Garcia Morin, C.B.B. Cristina Beléndez Bieler, E.B.C. Eduardo Bardón Cancho, J.H.A. Jorge Huerta Aragonés, C.M.F. Cristina Mata Fernández, C.G.C. Carmen Garrido Colino, E.C.O. Elena Carceller Ortega, O.A. Olalla Alvárez, A.B.M. Ana Belén Martínez, A.P. Ana Pérez, C.M. Cristina Muñoz, A.A. Alejandra Aguado, E.C.J. Elena Cela de Julián
Journal: HemaSphere (2023)

Background: Central nervous system (CNS) complications during hematopoietic stem cell transplantation (HSCT) in sickle cell disease (SCD) patients are a major cause of morbidity, as: posterior reversible encephalopathy syndrome (PRES), seizures, strokes or subarachnoid haemorrhage (HSA). These complications can appear for several causes, but mostly due to variations on hemodynamic status of the patient. Conditioning regimen-related toxicity, graft-versus-host disease (GvHD) and the use of calcineurin inhibitors also play an important role. Methods: A retrospective single center study was conducted in children with SCD, who underwent allogeneic HSCT from an HLA-identical sibling donor since January 2010 to July 2022. Implementation of arterial blood pressure (ABP) Holter, few weeks prior to HSCT, was established in December 2017 providing a better understanding of patient’s hemodynamic status and easing early treatment of arterial hypertension prior to HSCT. We analyze CNS transplant complications between two different periods: May 2010 to November 2017, and December 2017 to July 2022. Besides that, a change on conditioning regimen was established. Until June 2015 we used busulfan, cyclophosphamide and alemtuzumab. Afterwards, we changed to myeloablative but reduced toxicity conditioning: thiotepa, treosulfan, fludarabine, antithymocyte globulin. Also, GvHD prophylaxis used until 2019 was CsA and MTX, changing later to tacrolimus and mycophenolate mofetile (MMF). Seizure prophylaxis was provided during calcineurin inhibitors treatment, as well as maintenance of platelet threshold above 50.000/mcL, hemoglobin 11 g/dL and avoid hypomagnesemia. Epidemiological and clinical parameters were collected. Data are presented as percentages and quartiles. For the comparison of the variables under study, a bivariate analysis with non-parametric Fisher test was used. R Statistical Software was used for the numerical analysis and Survminer to represent Kaplan-Meier curves. Results: 50 allo-HCST were performed in 49 patients, median age 6.0 years (p25 2;p75 9). 22 patients in first period, 10 males (45%); and 27 patients in second, 15 males (55%). Prior to HSCT, 14/50 of HSCT had cerebrovascular disease (Moya-moya vasculopathy, silenct infarction, stroke or leukoencephalopathy); 64% (9/14) on first period and 36% (5/14) on second. During transplant, 11/50 had acute CNS complications: 91% (10/11) on first period (9/10 seizures, 5/10 HSA, 5/10 PRES and 1/10 other complications), and 9% (1/11) on second (mild toxicity to tacrolimus). HTA is present in 89% of total HSCT and in 100% with post-HSCT neurological complications, suggesting his major role in these type of situations. Global event-free survival of post-HSCT CNS complications at the end of follow-up period (12.5 years) was 77% (0.66-0.89). Statistically significant decrease on post-HSCT neurological complications on second period was observed compared to the first (seizures p<0.001; HSA p0.018; PRES p0.022), after the implementation of ABP Holter. Also, we couldn’t observe a statistically significant predisposition to have post-HSCT CNS complications according to their pre-neurological history. Conclusions: Even with reduced-toxicity conditioning and switch to tacrolimus, neurological events still happen. Mainly since the implementation of ABPH, our center have decreased acute CNS complications and improved SCD event-free survival rates during transplant, with less toxicity, morbidity and mortality. References 1. Shenoy S et al. Current Results and Future Research Priorities in Late Effects after Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease and Thalassemia. Biol Blood Marrow Transplant. 2017 Apr;23(4):552-561. 2. Krishnamurti L. Hematopoietic Cell Transplantation for Sickle Cell Disease. Front Pediatr. 2021 Jan 5;8:551170. 3. Walters MC et al. Neurologic complications after allogeneic marrowtransplantation for sickle cell anemia. Blood. 1995 Feb 15;85(4):879-84. 4. Farooq S et al. Neurologic Complications of Sickle Cell Disease. Curr Neurol Neurosci Rep. 2019 Feb 28;19(4):17. 5. Gluckman E et al. Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation. Blood. 2017 Mar 16;129(11):1548-1556.